Mitogen‐activated protein kinases (MAPKs) regulate normal brain functioning, and their dysfunction is implicated in a number of brain disorders. Thus, there is great interest in understanding the signalling systems that control MAPK functioning. One family of proteins that contribute to this process, the mitogen‐activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in foetal development, the immune system, cancer and synaptic plasticity and memory. In the present study, we performed an unbiased investigation using MKP‐2?/? mice to assess whether MKP‐2 plays a global role in modulating brain function. Local cerebral glucose utilization is significantly increased in the ventral tegmental area (VTA) of MKP‐2?/? mice, with connectivity analysis revealing alterations in VTA functional connectivity, including a significant reduction in connectivity to the nucleus accumbens and hippocampus. In addition, spontaneous excitatory postsynaptic current frequency, but not amplitude, onto putative dopamine neurons in the VTA is increased in MKP‐2?/? mice, which indicates that increased excitatory drive may account for the increased VTA glucose utilization. Consistent with modified VTA function and connectivity, in behavioural tests MKP‐2?/? mice exhibited increased sucrose preference and impaired amphetamine‐induced hyperlocomotion. Overall, these data reveal that MKP‐2 plays a role in modulating VTA function and that its dysfunction may contribute to brain disorders in which altered reward processing is present. 相似文献
Objective: Iron deficiency is the most common nutrient deficiency in the world. While deficiency can often be resolved through dietary supplementation with iron, adverse events are common and frequently preclude compliance. The objective of this study was to determine whether a food-derived dietary supplement containing a low dose of iron and nutrients that increase iron absorption could resolve iron deficiency with fewer adverse events than reported at higher doses.
Methods: A pilot clinical trial (NCT02683369) was conducted among premenopausal women with nonanemic iron deficiency that was verified by blood screening. Participants consumed a dietary supplement (Blood Builder®/Iron Response®) once daily for 8 weeks containing 26 mg of iron, vitamin C, folate, and other food-derived nutrients. Primary outcomes were markers of iron status (serum ferritin, hemoglobin, soluble transferrin receptor, total body iron stores) and secondary outcomes were self-reported fatigue and energy. All outcomes were assessed at baseline and 8 weeks. Adverse events were monitored with questionnaires, daily diaries, and contact with a physician. Dependent samples t test and Wilcoxon signed-rank test were used to analyze outcomes.
Results: Twenty-three participants enrolled in the study. Iron deficiency was resolved in the sample (mean serum ferritin: baseline = 13.9 μg/L, 8 weeks = 21.1 μg/L, p < 0.001). All other markers of iron status, fatigue, and energy also improved during the study (p < 0.04). No adverse events were reported. Conclusions: While larger and controlled studies are needed to confirm these findings, a food-derived dietary supplement with a low dose of iron and absorption-enhancing nutrients resolved iron deficiency and improved all other markers of iron status without any adverse events. 相似文献